Genetically modified rat models for pain

Abstract

This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in altered nervous system function. In one aspect, the altered function results in pain in the mammal. In another aspect, the nervous system dysfunction results in prolonged hyperalgesia, allodynia, and loss of sensory function. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of altered nervous system function mediated pain and methods of their use. In another aspect, the genetically modified rats, as well as the descendants and ancestors of such animals, are animal models of nervous system dysfunction resulting in prolonged hyperalgesia, allodynia, and loss of sensory function and methods of their use. In another aspect, the present invention provides a method of identifying a compound useful for the treatment or prevention of pain.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application Ser. No. 61 / 235,559, filed Aug. 20, 2009, which application is hereby incorporated by reference in its entirety for all purposes.BACKGROUND OF THE INVENTION[0002]Gene modification is a process whereby a specific gene, or a fragment of that gene, is altered. This alteration of the targeted gene may result in a change in the level of RNA and / or protein that is encoded by that gene, or the alteration may result in the targeted gene encoding a different RNA or protein than the untargeted gene. The modified gene may be studied in the context of a cell, or, more preferably, in the context of a genetically modified animal.[0003]Genetically modified animals are among the most useful research tools in the biological sciences. An example of a genetically modified animal is a transgenic animal, which has a heterologous (i.e., foreign) gene, or gene fragment, incorporated into...

AI Technical Summary

Problems solved by technology

This alteration of the targeted gene may result in a change in the level of RNA and / or protein that is encoded by that gene, or the alteration may result in the targeted gene encoding a different RNA or protein than the untargeted gene.

Visceral pain originates in the viscera (organs) and often is extremely difficult to locate, and several visceral regions produce “referred” pain when injured, where the sensation is located in an area distant from the site of injury or pathology

Sufferers are often stigmatized, because both medical professionals and the general public tend to think that pain from a psychological source is not “real”.

As a consequence, mutating both alleles to create a homozygous mutant animal is often required to produce a desired phenotype, since mutating one copy of a gene may not produce a sufficient change in the level of gene expression or activity of the gene product from that in the non-mutated or wild-type cell or multicellular organism, and since the remaining wild-type copy would still be expressed to produce functional gene product at sufficient levels.

In some instances, a mutation in both copies of a single gene will not be sufficient to create the desired physiological effects on the cell or multi-cellular organism.

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